Tissue oxygenation and perfusion and their interrelationships are among both the most important physiologic parameters and the most difficult to measure in vivo. During Phase I, we verified the feasibility of combining, in a miniature hybrid thermistor/polarographic sensor, both the unique capability of the Enhanced Thermal Diffusion Probe (ETDP) and recent advances in oxygen tension measurements. This Phase II development effort will be refine and improve the prototype probe/instrument system designed in Phase I to meet this critical need. The ETDP instrumentation will be expanded to include the measurement of tissue oxygen tension to +0.3 mmHg, adding to the measurement of temperature (+0.003oC) and perfusion (+10%), with appropriate isolation for medical applications. A platinum wire will be encapsulated in the glass coating of a thermistor bead, recessed electrochemically, and gold plated to serve as a flow-insensitive oxygen sensor. Aqueous gels will be used to fill the recess of the polarographic cathode to provide immunity to protein degradation. Oxygen tension and perfusion will be measured in either continuous or transient operational modes to provide both accuracy and flexibility. The temperature dependence of the oxygen tension measurement will be determined, and the measurement will be corrected in real time via software. This integrated system will permit investigation of perfusion, temperature, and oxygen tension (and their interrelationships) in the same small tissue volume. This capability is fundamental to many research and clinical studies, which include determination of the effectiveness of pharmacologic manipulations in different experimental and clinical states of circulatory shock (a condition responsible for over 250,000 Americans deaths yearly); examination of the effect of local perfusion and oxygen tension on ventricular arrhythmias; and monitoring of the various forms of thrombolytic therapy for coronary artery occlusion. Pre-commercial evaluation of this integrated hybrid system will be carried out by our Technology Assessment and Applications Group throughout Phase II.